CRES GENE IN MALE REPRODUCTION

男性生殖中的 CRES 基因

• 批准号: 2889236
• 负责人: Gail A Cornwall
• 金额: $ 10.43万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2889236
• 关键词: affinity chromatography; antibody; binding proteins; complementary DNA; crosslink; cysteine endopeptidases; electron microscopy; epididymis; genetic library; immunocytochemistry; intermolecular interaction; intracellular transport; laboratory mouse; laboratory rabbit; laboratory rat; light microscopy; male reproductive system; pituitary gland; posttranslational modifications; protease inhibitor; protein structure function; protein transport; regulatory gene; sperm; spermatogenesis

The overall objective of our studies is to determine the role of the novel CRES (cystatin-related epididymal-specific) protein in male reproductive function. The CRES protein exhibits a remarkably restricted pattern of expression and is highly regulated at the mRNA level by testicular factors. Of the 25 tissues examined, the male-specific CRES mRNA/protein has been localized to only the very proximal region of the caput epididymidis, the round/elongating spermatids of the testis, and to specific cells in the pituitary. The dramatic appearance and disappearance of the CRES protein in the testis and epididymis suggests that the protein may perform a specialized role during a very discrete phase of testicular and epididymal function. Furthermore, the homology of the CRES protein to the cystatin family of cysteine protease inhibitors, all of which are secretory binding proteins, suggests that it also may have protein binding activity. Indeed our preliminary studies suggest that CRES protein binds specifically to the head of the proximal caput epididymal spermatozoa in a very transient interaction. Therefore, our hypothesis is that the CRES protein may be a regulatory binding protein necessary for spermatogenic and sperm maturational events. Specifically, the CRES protein may bind to a sperm-associated protein, perhaps a protease. This binding may then result in the "activation" of the binding partner which subsequently may be critical for spermatogenic and sperm maturational events. To test our hypothesis we will: 1) extend our CRES protein localization studies by examining the cellular and intracellular localization of the CRES protein in the testis, epididymis, pituitary, and spermatozoa at the light and electron microscopic levels; 2) Isolate the rat CRES cDNA and prepare a rat CRES antibody for characterization of the rat CRES gene and protein; 3) begin CRES protein characterization studies by examining post-translational modifications of the CRES protein and cystatin activity; and 4) examine the interaction of CRES protein with mouse and rat sperm and initiate studies to identify the CRES protein binding partner. These studies will provide valuable information on a novel epididymal protein which may be important for sperm development and maturation.

我们研究的总体目的是确定新颖的作用 雄性生殖中的CRE（胱抑素相关的附睾特异性）蛋白 功能。 CRES蛋白表现出非常严格的限制模式 表达并通过睾丸在mRNA水平上受到高度调节 因素。 在检查的25个组织中，男性特异性CREMR​​NA/蛋白 仅定位到Caput的近端区域 附子，睾丸的圆形/拉长精子，至 垂体中的特定细胞。 戏剧性的外观和 睾丸和附睾中CRES蛋白的消失表明 蛋白质可以在非常离散的情况下发挥专业作用 睾丸和附睾功能的阶段。此外， CRES蛋白到半胱氨酸蛋白酶抑制剂的半胱氨酸蛋白酶家族， 所有这些都是分泌结合蛋白，表明它也可能 具有蛋白质结合活性。确实，我们的初步研究表明 CRES蛋白专门与近端caput的头部结合 瞬态相互作用中的附子精子。因此，我们的 假设是CRES蛋白可能是调节结合蛋白 精子和精子成熟事件所必需的。具体来说， CRES蛋白可能与精子相关蛋白结合，也许是 蛋白酶。这种结合可能会导致结合的“激活” 随后可能对精子和精子至关重要的伴侣 成熟事件。为了检验我们的假设，我们将：1）扩展我们的CRES 蛋白质定位研究通过检查细胞内和细胞内 CRE蛋白在睾丸，附睾，垂体和 精子在光和电子显微镜水平上； 2）隔离 大鼠CRES cDNA并制备大鼠cres抗体以表征 大鼠Cres基因和蛋白质； 3）开始CRES蛋白质表征研究 通过检查CRES蛋白的翻译后修饰和 半胱氨酸蛋白酶活性； 4）检查CRE蛋白与 小鼠和大鼠精子并开始研究以鉴定CRES蛋白 绑定伙伴。这些研究将提供有关 新型的附带蛋白可能对精子发育和 成熟。

项目成果

[Cres (cystatin-related epididymal spermatogenic) gene regulation and function]

Cres（胱抑素相关附睾生精）基因调控及功能]

• 发表时间: 2002
• 期刊: Zhonghua nan ke xue = National journal of andrology.
• 作者: Cornwall,GailA;Hsia,Nelson
• 通讯作者: Hsia,Nelson

Differential effects of GnRH and androgens on Cres mRNA and protein in male mouse anterior pituitary gonadotropes.

GnRH 和雄激素对雄性小鼠垂体前叶促性腺激素 Cres mRNA 和蛋白质的不同影响。

• DOI: 10.2164/jandrol.106.000331
• 发表时间: 2006
• 期刊: Journal of andrology
• 作者: Sutton-Walsh,HG;Whelly,Sandra;Cornwall,GailA
• 通讯作者: Cornwall,GailA

CCAAT/enhancer binding protein beta regulates expression of the cystatin-related epididymal spermatogenic (Cres) gene.

CCAAT/增强子结合蛋白β调节半胱氨酸蛋白酶抑制剂相关的附睾生精（Cres）基因的表达。

• DOI: 10.1095/biolreprod65.5.1452
• 发表时间: 2001
• 期刊: Biology of reproduction
• 影响因子: 3.6
• 作者: Hsia,N;Cornwall,GA
• 通讯作者: Cornwall,GA

Identification and characterization of cystatin-related epididymal spermatogenic protein in human spermatozoa: localization in the equatorial segment.

人类精子中半胱氨酸蛋白酶抑制剂相关附睾生精蛋白的鉴定和表征：定位于赤道段。

• DOI: 10.1095/biolreprod.102.003970
• 发表时间: 2002
• 期刊: Biology of reproduction
• 影响因子: 3.6
• 作者: Wassler,Michael;Syntin,Patrick;Sutton-Walsh,HG;Hsia,Nelson;Hardy,DanielM;Cornwall,GailA
• 通讯作者: Cornwall,GailA

ADAM7, a member of the ADAM (a disintegrin and metalloprotease) gene family is specifically expressed in the mouse anterior pituitary and epididymis.

• DOI: 10.1210/endo.138.10.5468
• 发表时间: 1997-10
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: G. Cornwall;N. Hsia